The dose effect of human bone marrow-derived mesenchymal stem cells on epidermal development in organotypic co-culture

F. Laco, M. Kun, H.J. Weber, S. Ramakrishna, C.K. Chan

    Research output: Contribution to journalArticle

    31 Citations (Scopus)

    Abstract

    BACKGROUND: A wealth of evidences have shown the participation and benefits of bone marrow-derived mesenchymal stem cells (BM-MSCs) in wound healing and skin tissue repair in vivo. However, their role in epidermal development and reconstitution is not clearly investigated. OBJECTIVE: Here we examine the quantitative effect of human BM-MSCs on epidermal regeneration in vitro. METHOD: Human keratinocytes and BM-MSCs are cultured at ratios from 0% to 100% on top of a fibroblast-embedded collagen gel in a three-dimensional organotypic co-culture model at an air-liquid interface up to 20 days and analyzed by histochemical and immunochemical staining of filaggrin, involucrin and keratin 10 on days 14 and 20. Human BM-MSCs were tracked with quantum dots in organotypic co-cultures. RESULTS: It was found that epidermal development is strongly influenced by the percentage of co-cultured BM-MSCs. A strong chemotactic effect between keratinocytes and MSCs was seen in the group with 50% of BM-MSCs, which resulted in an impaired epidermal development, whereas at a low percentage of BM-MSCs (10%), a stratified epidermal structure resembling native skin was established on day 14 of culture. Moreover, the immunostaining studies revealed that BM-MSCs in the low percentage (10%) participated in the basal periphery of reconstructed epidermis and a similar pattern characteristic of native epidermis was demonstrated in this experimental group, which was superior to all other experimental groups in terms of the thickness of stratum corneum and the expression profile of epidermal differentiation markers. CONCLUSION: This study indicates the advantage of using a new skin equivalent model incorporating a small fraction of MSCs to develop biologically useful tissues for maintaining homeostasis during skin regeneration and wound healing process.
    LanguageEnglish
    Pages150-160
    Number of pages10
    JournalJournal of Dermatological Science
    Volume55
    Issue number3
    DOIs
    Publication statusPublished - Sep 2009

    Fingerprint

    Coculture Techniques
    Mesenchymal Stromal Cells
    Bone Marrow
    Skin
    Keratinocytes
    Epidermis
    Wound Healing
    Regeneration
    Keratin-10
    Quantum Dots
    Differentiation Antigens
    Cornea
    Homeostasis
    Collagen
    Fibroblasts
    Gels
    Air
    Staining and Labeling

    Keywords

    • mesenchymal stem cells
    • organotypic
    • epidermis
    • skin regeneration

    Cite this

    Laco, F. ; Kun, M. ; Weber, H.J. ; Ramakrishna, S. ; Chan, C.K. / The dose effect of human bone marrow-derived mesenchymal stem cells on epidermal development in organotypic co-culture. In: Journal of Dermatological Science . 2009 ; Vol. 55, No. 3. pp. 150-160.
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    abstract = "BACKGROUND: A wealth of evidences have shown the participation and benefits of bone marrow-derived mesenchymal stem cells (BM-MSCs) in wound healing and skin tissue repair in vivo. However, their role in epidermal development and reconstitution is not clearly investigated. OBJECTIVE: Here we examine the quantitative effect of human BM-MSCs on epidermal regeneration in vitro. METHOD: Human keratinocytes and BM-MSCs are cultured at ratios from 0{\%} to 100{\%} on top of a fibroblast-embedded collagen gel in a three-dimensional organotypic co-culture model at an air-liquid interface up to 20 days and analyzed by histochemical and immunochemical staining of filaggrin, involucrin and keratin 10 on days 14 and 20. Human BM-MSCs were tracked with quantum dots in organotypic co-cultures. RESULTS: It was found that epidermal development is strongly influenced by the percentage of co-cultured BM-MSCs. A strong chemotactic effect between keratinocytes and MSCs was seen in the group with 50{\%} of BM-MSCs, which resulted in an impaired epidermal development, whereas at a low percentage of BM-MSCs (10{\%}), a stratified epidermal structure resembling native skin was established on day 14 of culture. Moreover, the immunostaining studies revealed that BM-MSCs in the low percentage (10{\%}) participated in the basal periphery of reconstructed epidermis and a similar pattern characteristic of native epidermis was demonstrated in this experimental group, which was superior to all other experimental groups in terms of the thickness of stratum corneum and the expression profile of epidermal differentiation markers. CONCLUSION: This study indicates the advantage of using a new skin equivalent model incorporating a small fraction of MSCs to develop biologically useful tissues for maintaining homeostasis during skin regeneration and wound healing process.",
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    The dose effect of human bone marrow-derived mesenchymal stem cells on epidermal development in organotypic co-culture. / Laco, F.; Kun, M.; Weber, H.J.; Ramakrishna, S.; Chan, C.K.

    In: Journal of Dermatological Science , Vol. 55, No. 3, 09.2009, p. 150-160.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - The dose effect of human bone marrow-derived mesenchymal stem cells on epidermal development in organotypic co-culture

    AU - Laco, F.

    AU - Kun, M.

    AU - Weber, H.J.

    AU - Ramakrishna, S.

    AU - Chan, C.K.

    PY - 2009/9

    Y1 - 2009/9

    N2 - BACKGROUND: A wealth of evidences have shown the participation and benefits of bone marrow-derived mesenchymal stem cells (BM-MSCs) in wound healing and skin tissue repair in vivo. However, their role in epidermal development and reconstitution is not clearly investigated. OBJECTIVE: Here we examine the quantitative effect of human BM-MSCs on epidermal regeneration in vitro. METHOD: Human keratinocytes and BM-MSCs are cultured at ratios from 0% to 100% on top of a fibroblast-embedded collagen gel in a three-dimensional organotypic co-culture model at an air-liquid interface up to 20 days and analyzed by histochemical and immunochemical staining of filaggrin, involucrin and keratin 10 on days 14 and 20. Human BM-MSCs were tracked with quantum dots in organotypic co-cultures. RESULTS: It was found that epidermal development is strongly influenced by the percentage of co-cultured BM-MSCs. A strong chemotactic effect between keratinocytes and MSCs was seen in the group with 50% of BM-MSCs, which resulted in an impaired epidermal development, whereas at a low percentage of BM-MSCs (10%), a stratified epidermal structure resembling native skin was established on day 14 of culture. Moreover, the immunostaining studies revealed that BM-MSCs in the low percentage (10%) participated in the basal periphery of reconstructed epidermis and a similar pattern characteristic of native epidermis was demonstrated in this experimental group, which was superior to all other experimental groups in terms of the thickness of stratum corneum and the expression profile of epidermal differentiation markers. CONCLUSION: This study indicates the advantage of using a new skin equivalent model incorporating a small fraction of MSCs to develop biologically useful tissues for maintaining homeostasis during skin regeneration and wound healing process.

    AB - BACKGROUND: A wealth of evidences have shown the participation and benefits of bone marrow-derived mesenchymal stem cells (BM-MSCs) in wound healing and skin tissue repair in vivo. However, their role in epidermal development and reconstitution is not clearly investigated. OBJECTIVE: Here we examine the quantitative effect of human BM-MSCs on epidermal regeneration in vitro. METHOD: Human keratinocytes and BM-MSCs are cultured at ratios from 0% to 100% on top of a fibroblast-embedded collagen gel in a three-dimensional organotypic co-culture model at an air-liquid interface up to 20 days and analyzed by histochemical and immunochemical staining of filaggrin, involucrin and keratin 10 on days 14 and 20. Human BM-MSCs were tracked with quantum dots in organotypic co-cultures. RESULTS: It was found that epidermal development is strongly influenced by the percentage of co-cultured BM-MSCs. A strong chemotactic effect between keratinocytes and MSCs was seen in the group with 50% of BM-MSCs, which resulted in an impaired epidermal development, whereas at a low percentage of BM-MSCs (10%), a stratified epidermal structure resembling native skin was established on day 14 of culture. Moreover, the immunostaining studies revealed that BM-MSCs in the low percentage (10%) participated in the basal periphery of reconstructed epidermis and a similar pattern characteristic of native epidermis was demonstrated in this experimental group, which was superior to all other experimental groups in terms of the thickness of stratum corneum and the expression profile of epidermal differentiation markers. CONCLUSION: This study indicates the advantage of using a new skin equivalent model incorporating a small fraction of MSCs to develop biologically useful tissues for maintaining homeostasis during skin regeneration and wound healing process.

    KW - mesenchymal stem cells

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    KW - epidermis

    KW - skin regeneration

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    VL - 55

    SP - 150

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    JO - Journal of Dermatological Science

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    SN - 1873-569X

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    ER -